Hapln1b, a central organizer of the ECM, modulates kit signaling to control developmental hematopoiesis in zebrafish

Christopher B. Mahony*, Pietro Cacialli, Corentin Pasche, Rui Monteiro, Savvas N. Savvides, Julien Y. Bertrand

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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During early vertebrate development, hematopoietic stem and progenitor cells (HSPCs) are produced in hemogenic endothelium located in the dorsal aorta, before they migrate to a transient niche where they expand to the fetal liver and the caudal hematopoietic tissue, in mammals and zebrafish, respectively. In zebrafish, previous studies have shown that the extracellular matrix (ECM) around the aorta must be degraded to enable HSPCs to leave the aortic floor and reach blood circulation. However, the role of the ECM components in HSPC specification has never been addressed. In this study, hapln1b, a key component of the ECM, was specifically expressed in hematopoietic sites in the zebrafish embryo. Gain- and loss-of-function experiments all resulted in the absence of HSPCs in the early embryo, showing that hapln1b is necessary, at the correct level, to specify HSPCs in the hemogenic endothelium. Furthermore, the expression of hapln1b was necessary to maintain the integrity of the ECM through its link domain. By combining functional analyses and computer modeling, we showed that kitlgb interacts with the ECM to specify HSPCs. The findings show that the ECM is an integral component of the microenvironment and mediates the cytokine signaling that is necessary for HSPC specification.

Original languageEnglish
Pages (from-to)4935–4948
Number of pages14
JournalBlood Advances
Issue number23
Early online date20 Sept 2021
Publication statusPublished - 14 Dec 2021

Bibliographical note

Funding Information:
J.Y.B. holds a Chair in Life Sciences funded by the Gabriella Giorgi-Cavaglieri Foundation and is also funded by the Swiss National Fund (310030_184814) and the “Fondation Privée des HUG”. R.M. and C.B.M. were funded by a British Heart Foundation IBSR Fellowship (FS/13/50/30436).

Publisher Copyright:
© 2021 by The American Society of Hematology.

ASJC Scopus subject areas

  • Hematology


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